Review supports casein hydrolysate as blood pressure intervention

Researchers conducted what they believe to be the first such review on available randomized controlled trials (RCTs) investigating the implications of supplementation on CVD risk factors.

The comprehensive assessment validates data demonstrating reductions in systolic and diastolic BP in participants (by 3.20 millimetres of mercury (mmHg) and 1.5 mmHg, respectively), irrespective of age, duration of intervention, preparation, or disease status, the authors write.

“Our findings have certain public health implications, and casein hydrolysate combined with other food-effective nutrients may generate potential synergistic effects on improving human health,” ​they assert.

CVD risks​

Casein in milk protein is a rich source of common and essential amino acids. Regular consumption slows protein digestion and reduces catabolic activity. Casein-derived hydrolysate exhibits additional functionality, including anti-inflammatory, antioxidant, and antihypertensive activity.

A healthy diet is recommended as a preventative measure to reduce CVD incidence and milk protein supplements are considered an effective dietary approach to lower BP.

CVD is the leading cause of mortality worldwide, the authors say. Indeed, 2021 figures from the World Health Organisation (WHO) indicate CVD deaths have increased by one quarter since 2000, with 17.9 million documented cases in 2019 and predictions of 22.2 million by 2030.

They comment: “Although a variety of foods with cardioprotective potentials have been identified by epidemiological Studies, the optimal nutrient composition for CVD remain to be investigated.”​

Review protocol​

The systemic assessment and meta-analysis on the effects of casein hydrolysate on CVD risk factors was performed according to PRISMA guidelines. In total, researchers identified 26 articles and 33 trials sourced from PubMed and Web of Science databases.

Inclusion criteria were random-controlled trials analysing casein hydrolysate or lactotripeptides in humans, using a comparable placebo or control group. Articles had to be published in English and report at least one CVD risk factor.

Two independent reviewers assessed the risk of bias based on Cochrane Collaboration Handbook recommendations.

Effects of casein hydrolysate on systolic BP (SBP), diastolic BP (DBP), triglycerides (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and fasting blood glucose (FBG) were evaluated.

Vasodilative effect​

A stratified analysis of 30 trials showed improved BP outcomes in participants with elevated and normal baseline SBP and DBP, in younger (-50 years) versus older participants, and healthy versus participants with BP disorders.

The BP decreasing mechanism of casein hydrolysate relates to bioactive peptides released during fermentation or enzymatic preparation, such as isoleucine-proline-proline and valine-proline-proline, the authors explain.

“These bioactive peptides were shown to have a vasodilative effect by inhibiting angiotensin I-converting enzyme (ACE) activity in human interventional studies. ACE is the critical enzyme converting angiotensin I into the vasoconstrictor angiotensin II, making vasodilator bradykinin inactivation and eliciting BP elevation.”​

Bioactive peptides also inhibit renin and endothelin-converting enzyme activity, that modulate “sympathetic nervous activity​”, to reduce BP and display preventive effects on cerebrovascular aging and neurovascular diseases.

Consistent findings​

Results demonstrating SBP and DBP reductions were the same in short-term (up to eight weeks) and long-term interventions, as were findings for fermented or enzymatic preparations.

There were no reported effects of supplementation on total cholesterol, LDL and HDL cholesterol, FBG, or TC, compared with the placebo. Sensitivity analysis indicated results for SBP, DBP, TC and FBG were reliable.

Overall, “findings suggest that casein hydrolysate supplementation is beneficial for blood pressure control, consistent with previous systematic reviews,”​ the authors write.

Research limitations include the small number of RCTs, limited information on random sequency generation and allocation concealment, and heterogeneity and publication bias.

Source: Nutrients​

Published online, October 9, 2022: http://doi.org/10.3390/nu14194207​

‘Effect of Casein Hydrolysate on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials’​

Authors: Shuaishuai Zhou, Teng Xu, Xu Zhang, Junjie Luo, Peng An and Yongting Luo